Glucocorticosteroids, which have anti-inflammatory and anti-allergy properties, are well known and are widely used to treat conditions requiring an anti-inflammatory and/or anti-allergic response. One such class of glucocorticosteroids having such properties are androstane steroids of the type disclosed in U.S. Pat. No. 4,335,121, and particularly fluticasone esters, and more particularly fluticasone propionate, namely 6α,9α-difluoro-17α(1-oxopropoxy)-11β-hydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester, and derivatives thereof. In this regard, CULTIVATE® topical cream and ointment, containing 0.05% and 0.005% fluticasone propionate respectively, is marketed by GlaxoSmithKline. These products have anti-inflammatory, anti-pruritic and vasoconstrictive properties.
It has been desirable to increase the activity of the active ingredient in such formulations. By increasing the vasoconstrictor potency, the effectiveness of the active ingredient is increased. In International Patent application Publication No. WO 00/24401 it is taught that increased vasoconstrictor potency of fluticasone propionate lotion formulations over fluticasone propionate cream formulations is obtained at decreased concentrations of occlusive agent, i.e., under 10 w/w %. However, it is recognized that the addition of an occlusive agent, such as mineral oil or paraffin, increases the vasoconstrictor potency of topical steroids. Yet, high concentrations of occlusive agents can cause the formulation to be unstable, and invert an oil-in-water emulsion to a greasy feeling water-in-oil emulsion.
In order to still obtain the high vasoconstrictor potency of such a the formulation, while avoiding the instability problem of the product, and still have a relatively high level of occlusive agent in the product, it has been proposed in International patent Publication No. WO 02/13868, to employ a specific type of surfactant system, namely one wherein the surfactant system employed in the formulation must have an HLB value ranging from about 7.0 to about 10.9 and with the surfactant system being present in the formulation in a w/w % amount of from about 0.25 to about 10.0. Also, in United States Patent Application Publication Nos. 2003/0130247 A1, 2003/0176408 A1 and 2003/0186951 A1 it is suggested to employ very high amounts of a penetration enhancer, such as propylene glycol, such that the ratio of the penetration enhancer to a total of the penetration enhancer, solvents and emulsifiers is at lest about 0.70, preferably at least about 0.80 and most preferably about 0.90 or 0.95, so as to obtain enhanced vasoconstriction activity or potency. However, it is desirable to be able to obtain such increased or even better vasoconstriction potency for such androstane-containing topical formulations without the necessity for using such high levels of penetration enhancers.
Thus, there is still a need for better, more reliable topical formulations where the amount of active ingredient available for vasoconstrictor activity is increased and without requiring undue limitations on the compositions of the formulations. Hence, there is a need for such topical formulation where the amount of active ingredient soluble in the solvent system of the formulation is increased and thereby the vasoconstrictor activity or potency of the formulation is increased.